This is one of the first studies to demonstrate both feasibility and clinically important improvements from a dietary change in metastatic breast cancer patients receiving systemic therapy. Results from this study showed that our whole-food, plant-based dietary intervention promotes significant weight loss and improves several cardiometabolic and hormonal risk factors among women with metastatic breast cancer. Specifically, subjects in the intervention group, who had a baseline BMI of 29.7 kg/m2, lost 1–2 pounds a week and saw significant improvements, both clinically and statistically, in cholesterol, insulin, insulin resistance, sex hormone binding globulin, and IGF-1.
Several other nutrition and lifestyle trials for cancer survivors, conducted after subjects had completed their primary cancer treatment, have demonstrated feasibility and weight loss, but most show lower or significantly slower weight loss than this trial[31–40]. Weight loss in this study reflects the large nutritional changes achieved, described in a separate report [REF]. While this amount of weight loss may be larger and/or faster compared to previous cancer interventions, the rate of weight loss is consistent with other interventions using whole-food, plant-based diets, even when no prepared food is provided[18, 42]. It is also consistent with recommendations for individuals with excess weight in the general population to target 1 to 2 pounds of weight loss per week during their weight loss efforts[43].
The weight loss was due to large, intentional dietary changes, without signs or symptoms of concurrently progressing disease or cachexia, and it was achieved without portion or calorie restriction or mandated exercise. Coaching included frequent recommendations to eat greater volumes of food and eat more frequently, while choosing foods that were ‘on plan’. When comparing the final 3-day food diary with the baseline 3-day food diary, intervention subjects had 16% greater dietary intake (solid plus liquid intake) in terms of weight but consumed 26% fewer calories, suggesting significantly reduced calorie density of the study diet compared to their baseline diets.
Consistent with weight loss, the cardiometabolic and hormonal milieu improved within the intervention group. These changes likely relate to a convergence of mechanisms. While weight loss itself can result in positive changes in some of these markers, the plant-based dietary composition also likely played a role. Dietary patterns with substantial increases in dietary fiber and substantial reductions in saturated fat and/or animal protein have been tested in various human trials and found to modulate serum cholesterol[44, 45], insulin resistance[46, 47], sex hormones[48–50], and IGF-1[51].
Whether this weight loss or risk factor modification improves cancer-specific progression or mortality is unknown. Barnard, et al.[52] found that, in post-menopausal women with overweight or obesity, a 2-week intervention consisting of an ad libitum whole-food, plant-predominant diet and exercise resulted in significantly reduced estradiol, insulin, and IGF-1. When comparing subjects’ pre- and post-intervention serum in vitro, using 3 estrogen receptor-positive breast cancer cell lines, there was a significant decrease in cell growth and increase in apoptosis concurrent with improvements in biomarkers following the diet and lifestyle intervention.
In our study, there were no significant changes in cancer markers at 8 weeks, although the intervention group showed a more stable trend compared to the control group. Among participants who did not have elevated cancer markers during the study, 50% of control participants and 46% of intervention participants previously had elevated markers, suggesting relatively similar percentage of participants in both groups who had cancer markers that reflected cancer activity. Both normal baseline levels among the intervention group along with our small sample size limited our ability to detect larger changes. In addition, the short duration of the trial makes changes in cancer markers more difficult to interpret given the possibility of spurious results in the first 4–6 weeks following therapy changes[53].
This randomized controlled trial has numerous limitations and strengths. The study duration limits our ability to know whether these findings are sustainable, and whether these findings affect risks of cancer progression or mortality. The size of the study, particularly the smaller control group, limits our ability to detect smaller differences in outcomes. In addition, the lack of racial diversity as well as the overrepresentation of hormone-receptor positive breast cancer both limit generalizability. The control group was not matched in terms of time with, and attention from, study staff, making it harder to isolate the effects of the dietary changes from the effects of the overall intervention. Strengths of the study include the very large dietary changes achieved and high retention rate, presumably related to the intensity of the intervention and the provided food.